DERIVATIZED 3,4-ALKYLENEDIOXYTHIOPHENE MONOMERS, METHODS OF MAKING THEM, AND USE THEREOF

Description

FIELD OF THE DISCLOSURE

[0001] The present invention is directed to processes for preparing derivatized 3,4-alkylenedioxythiophenes having improved solubility in water.

BACKGROUND

[0002] Poly(3,4-ethylenedioxythiophene) (PEDOT) is an important electrically conductive polymer because of both its high conductivity and temperature stability. Its monomeric unit, 3,4-ethylenedioxythiophene (EDOT), however, has poor solubility in water. While some water-soluble EDOT compounds are known in the art, such as EDOT-CH₂OH, the known method of making EDOT-CH₂OH involves a complex series of six reaction steps starting from thiodiglycolic acid. Thus, a need exists for improved processes for making derivatized EDOT compounds having improved solubility in water.

[0003] The synthesis and polymerisation of new monomers derived from 3,4-ethylenedioxythiophene has been described by Schottland et al. in Journal de Chimie Physique, 1998,95, 1258-1261.

SUMMARY

[0004] Provided are methods of making derivatized 3,4-alkylenedioxythiophene compounds.

[0005] In one embodiment, the present invention comprises a process for preparing a compound of Formula I:

wherein n is from 1 to 4, comprising contacting a compound of Formula II:

wherein X is halogen and n is from 1 to 4; with an inorganic hydroxide, an alkali or alkaline earth metal carboxylate, or an ammonium or alkylammonium carboxylate.

[0006] The

of Formula II can be a straight chain or branched. In some embodiments, the group can be substituted with moieties which do not interefere with the chemistry in the process for forming the compound with Formula I. In some embodiments, the substituents may also improve solubility, such as, for example, ether, ester, or carboxylate groups.

[0007] In one embodiment, the present invention comprises a process for preparing a compound of Formula II:

comprising contacting a 3,4-dialkoxythiophene with an ω-halo-1,2-alkanediol in the presence of an acid. In certain embodiments, the ω-halo-1,2-alkanediol is a 3- halo-1,2-propanediol.

[0008] The foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention, as defined in the appended claims

DETAILED DESCRIPTION

[0009] Provided are processes for preparing derivatized 3,4-alkylenedioxythiophene compounds.
An exemplary derivatized 3,4-alkylenedioxythiophene compound made by the methods of the present invention is (2,3-dihydrothieno[3,4-b][1,4]dioxin-3-yl)methanol, or EDOT-CH₂OH.

[0010] For use herein, the term EDOT-CE₂OH refers to a compound of Formula III:

[0011] In one embodiment, the present invention is directed to processes for preparing derivatized 3,4-alkylenedioxythiophene compounds comprising contacting a compound of Formula II:

wherein X is halogen and n is from 1 to 4, with an inorganic hydroxide, alkali metal carboxylate, alkaline earth metal carboxylate, or ammonium or alkylammonium carboxylate, to provide a compound of Formula I wherein n is from 1 to 4:

[0012] In one embodiment, n is 1 and the derivatized 3,4-alkylendioxythiophene compound is EDOT-CH₂OH

[0013] In one embodiment, the inorganic hydroxide is an alkali metal hydroxide, an alkaline earth metal hydroxide, or an ammonium or alkylammonium hydroxide. Exemplary alkali metal hydroxides include, for example, KOH, NaOH, or LiOH. Exemplary alkaline earth metal hydroxides include, for example, Mg(OH)₂ or Ca(OH)₂.

[0014] In one embodiment, the contacting step is performed in the presence of a catalyst. The catalyst can be any molecule capable of facilitating the synthesis reaction. In some exemplary embodiments, the catalyst is a crown ether. For use herein, the term crown ether refers to a macrocyclic polyether whose structure exhibits a conformation with a so-called hole capable of trapping cations by coordination with a lone pair of electrons on oxygen atoms. Each oxygen atom is bound between two of the carbons atoms and arranged in a ring. Exemplary crown ethers for use herein include 18-crown-6, 15-crown-5, 12-crown-4 or a combination thereof.

[0015] In one embodiment, the conversion of a compound of Formula II to a derivatized 3,4-alkylenedioxythiophene compound, such as a 3,4- alcohol, is by a substitution reaction. A substitution reaction involves replacement of a leaving group by another functional group. In one aspect, a substitution reaction entails reacting a compound of Formula II with an hydroxide salt in one or more polar aprotic solvents. In some exemplary embodiments, the one or more crown ethers, one or more cryptands, sodium iodide, or a combination thereof can be used as catalysts. The term cryptands refers to a macropolycyclic polyazo-polyether, where the three-coordinate nitrogen atoms provide the vertices of a three-dimentional structure. Exemplary cryptands include, for example, 4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane.

[0016] In one embodiment, the conversion of a compound of Formula II to a derivatized 3,4-alkylenedioxythiophene compound, such as a 3,4-alkylenedioxythiophene alcohol, is by a two-step procedure. The first step is a substitution reaction using the salt of a carboxylic acid, e.g., sodium acetate, potassium acetate, ammonium acetate, sodium benzoate, potassium benzoate, and ammonium benzoate, in one or more polar aprotic solvents to form an organic ester. The ester can then be hydrolyzed to form the corresponding 3,4-alkylenedioxythiophene alcohol.

[0017] Also provided are processes for preparing a compound of Formula II

wherein X is halogen and n is from 1 to 4, comprising contacting a 3,4-alkylenedioxythiophene with a halo-1,2-alkanediol in the presence of an acid. In one embodiment, the halo-1,2-alkanediol has the formula CH₂(OH)CH(OH)(CH₂)_nX, where n is from1 to 4. Exemplary acids include, but are not limited to, para-toluenesulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid, trifluoroacetic acid, sulfuric acid, or any combination thereof.

[0018] In one embodiment, n is 1 and the 3,4-alkylenedioxythiophene is contacted with 3-halo-1,2,-propanediol. In embodiments, wherein n is 2, 3, or 4, 3,4-alkylenedioxythiophene can be contacted with other halo-1,2,-alkanediols including, for example, 3-bromo-1,2-propanediol, 4-bromo-1,2-butanediol, 5-bromo-1,2-pentanediol, and the like. Halo-1,2,-alkanediols are readily available from commercial sources, such as Aldrich Company, Milwaukee, Wisconsin, USA." can be synthesized according to methods known in the art (Journal of Catalysis, 208(2), 339-344, 2002; Synthesis, (4), 295-7, 1989), or through direct oxidation of ω-bromo-α-olefins using an oxidizing agent such as potassium permanganate or osmium tetroxide.

[0019] In one embodiment, the contacting step is performed in the presence of a solvent. Exemplary solvents include, but are not limited to aralkanes. In one embodiment of the present invention, the aralkane is toluene. Exemplary 3-halo-1,2-propanediols include 3-chloro-1,2-propanediol and 3-bromo-1,2-propanediol.

[0020] In one embodiment, provided are processes for preparing a derivatized 3,4-alkylenedioxythiophene comprising contacting 3,4-dihalothiophene, e.g., 3,4-dibromothiophene, with an alkoxide in the presence of copper and iodine reagents. In one embodiment, the 3,4-dialkoxythiophene is 3,4-dimethoxythiophene. Exemplary alkoxides include, but are not limited to, sodium or potassium methoxide. The copper and iodine reagents can be any compound capable of facilitating the synthesis reaction. In an exemplary embodiment, the reagents are copper(II) oxide and potassium iodide. (Both need to be present for the reaction to work.) In one embodiment, the contacting step is performed in the presence of a solvent. Exemplary solvents include, for example, alkanols. Exemplary alkanols include, for example, methanol. In one aspect, the process is carried out at reflux. In one embodiment, the reaction is conducted under an inert atmosphere of nitrogen, argon, or a combination thereof.

[0021] Accordingly, provided are methods for preparing derivatized 3,4-alkylenedioxythiophene compounds comprising contacting a 3,4-alkylenedioxythiophene with a halo-1,2-alkanediol in the presence of an acid to form a compound of Formula II

wherein X is halogen and n is from 1 to 4; and subsequently contacting a compound of Formula II with an inorganic hydroxide, alkali metal carboxylate, alkaline earth metal carboxylate, or ammonium or alkylammonium carboxylate, to form a compound of Formula I:

[0022] In one aspect, the derivatized 3,4-alkylenedioxythiophene is prepared by contacting a 3,4-dihalothiophene with an alkoxide in the presence of copper and iodine reagents.

[0023] In one embodiment, provided are methods for preparing EDOT-CH₂OH comprising contacting 3,4-dialkoxythiophene with 3-halo-1,2-propanediol in the presence of an acid to form a compound of Formula IV:

wherein X is halogen; and subsequently contacting a compound of Formula IV with an inorganic hydroxide, ammonium or alkylammonium hydroxide, alkali metal carboxylate, alkaline earth metal carboxylate, or ammonium or alkylammonium carboxylate, to form EDOT-CH₂OH. In one embodiment, the 3,4-dialkoxythiophene is prepared by contacting a 3,4-dihalothiophene with an alkoxide in the presence of copper and iodine containing reagents.

[0024] Also provided are compounds of Formula IV

wherein X is Halogen.

[0025] A representative synthetic scheme of the present invention is provided below as Scheme L Scheme 1 demonstrates exemplary processes for the preparation of EDOT-CH₂OH ((2,3-dihydro-thieno[3,4-b][1,4]dioxin-2-yl) methanol). The skilled practitioner will know how to make use of variants of these process steps. In this representative scheme, treatnent of 3,4-dihalothiophene with an alkoxide base in the presence of copper(II) oxides and potassium iodide provides the corresponding 3,4-alkylenedioxythiophene. Reaction of 3,4-dialkoxythiophene with 3-halo-1,2-propanediol in the presence or an acid, such as para-toluenesulfonic acid, or the like, gives rise to a halomethyl derivatized EDOT. Subsequent reaction of the halo derivative with, for example, an alkali metal hydroxide, alkaline earth metal hydroxide, ammonium or alkylammonium hydroxide, alkali metal carboxylate, alkaline earth metal carboxylate, or ammonium or alkylammonium carboxylate, converts the halo-EDOT to hydroxy-EDOT.

[0026] Compounds having Formula I are referred to collectively as "derivatized 3,4-alkylenedioxythiophene compounds".

[0027] Other features and benefits of any one or more of the embodiments will be apparent from the following detailed description, and from the claims. The detailed description first addresses Definitions and Clarification of Terms followed by the Illustrative Electronic Devices, and finally Examples.

1. Definitions and Clarification of Terms

[0028] Before addressing details of embodiments described below, some terms are defined or clarified.

[0029] As used *herein, the terms "comprises," "comprising," "includes," "including," "has," "having" or any other variation thereof, are intended to cover a non-exclusive inclusion. For example, a process, method, particle, or apparatus that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. Further, unless expressly stated to the contrary, "or" refers to an inclusive or and not to an exclusive or. For example, a condition A or B is satisfied by any one of the following. A is true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and both A and B are true (or present).

[0030] Also, use of "a" or "an" we employed to describe elements and components of the invention. This is done merely for convenience and to give a general sense of the invention. This description should be read to include one or at least one and the singular also includes the plural unless it is obvious that it is meant otherwise.

[0031] The term "halogen" or "halo" refers to chlorine, bromine, fluorine, and iodine.

[0032] "Aralkane" refers to a moiety composed of an alkane bearing an aryl substituent or to a cycloalkane fused to an aryl ring and having from about 6 to about 20 carbon atoms (and all combinations and subcombinations of ranges and specific numbers of carbon atoms therein), with from about 6 to about 10 carbon atoms being preferred. Non-limiting examples include, for example, toluene, ethyl benzene, mesitylene, tetralin, cumene, cymene, methylnaphthalene, and diphenylmethane.

[0033] The term "colloid" or "colloidal" refers to the minute particles suspended in a continuous liquid medium, said particles having a nanometer-scale particle size. The term "colloid-forming" refers to substances that form minute particles when dispersed in a liquid medium, i.e., "colloid-forming" materials are not soluble in the liquid medium.

[0034] "Alkyl" refers to an optionally substituted, saturated straight, branched, or cyclic hydrocarbon radical having from about 1 to about 20 carbon atoms (and all combinations and subcombinations of ranges and specific numbers of carbon atoms therein). Alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, isohexyl, 3-methylpentyl, 2,2-dimethylbutyl, and 2,3-dimethylbutyl.

[0035] "Alkoxide" refers to an alkyl-O- anion, wherein alkyl is as previously defined. Alkoxide is generally associated with a cationic counterion, such as Na+, K+, Li+, Mg++, Ca++, ammonium, alkylammonium, and the like on an equivalent charge basis. Exemplary alkoxides include, for example, methoxide, ethoxide, n-propoxide, i-propoxide, n-butoxide, and heptoxide.

[0036] "Alkanol" refers to alkyl alcohols, such as those provided by protonation of alkoxides, wherein alkyl is as previously defined.

[0037] "Halo" refers to a fluoro, chloro, bromo, or iodo moiety.

[0038] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonty understood by one of ordinary skill in the art to which this invention belongs.

EXAMPLES

[0039] Example A provides a method for the prior art method of synthesizing EDOT-CH₂OH for comparative purposes. Examples 1 through 13 provide representative methods of the present invention.

Example A:

[0040] Synthesis of 3,4-ethylenedioxythiophene methanol is adapted from the publication "Electropolymerization of and 3,4-ethylenedioxythiophene ethanol in the presence of dodecylbenzenesulfonate", Lima A, Schouland P, Sadici A. Chevrot C; Synth. Met. 1998, 93, 33-41.

1) Synthesis of diethyl thiodiglycolate

[0041] In a 2-necked round bottom flask equipped with a reflux condenser and an equilibrium addition funnel 100 g (0.667 mol) thiodiglycolic acid was dissolved in 500 mL refluxing ethanol. The equilibrium addition funnel was charged with 40 mL concentrated sulfuric acid. The acid was added dropwise and the reaction refluxed overnight. Upon cooling the reaction to room temperature it was carefully poured into 600 mL water. The product was extracted with diethyl ether until the ether wash no longer contained the desired product. The organic extracts were washed with a saturated sodium bicarbonate solution three times. Upon drying with magnesium sulfate and solvent removal under reduced pressure a colorless oil was isolated (131.3 g, 95% yield). Structure and purity were confirmed by ¹H/¹³C NMR and GC-MS.

2) Synthesis of diethyl 3,4-dihydroxythiophene-2,5-dicarboxylate

[0042] In a 2 L two-necked flask equipped with a reflux condenser 175 g (2.57 mol) of sodium ethoxide was dissolved in 1200 mL anhydrous ethanol. The reaction was cooled to 0 C and a solution of 106 g (0.514 mol) diethylthioglycolate and 188 g (1.28 mol) diethyl oxalate in ethanol was added dropwise. Upon completion of the addition, the cooling bath was removed and the reaction heated to reflux overnight. The reaction was then cooled-to room temperature and filtered. The resulting yellow solid was washed with ethanol and allowed to dry. The solid was split into two portions and each was added to a large Erlenmeyer flask with water to make a suspension upon stirring. Acidification with HCl provided a white solid. The solid was filtered and allowed to dry under vacuum to give 80g (60% yield) of product as a white powder. Further material can be isolated by cooling the mother liquor and subsequent filtration. Structure and purity were confirmed by ¹H/¹³C NMR and LC-MS.

3) Synthesis of diethyl 2,3-dihydro-2-(hydroxymethyl)thieno[3,4-b][1,4]dioxine-5,7-dicarboxylate

[0043] 7.7 mL (0.0902 mol) of epibromohydrin and 1.92 g (0.0139 mol) of potassium carbonate were dissolved in 100 mL water and added to a refluxing mixture of 16.11 g (0.0694 mol) diethyl 3,4-dihydroxythiophene-2.5-dicarboxylate in 350 mL ethanol. After heating to reflux for 1 hour, an additional 5.3 mL (0.0624 mol) epibromohydrin was added and the reaction heated to reflux overnight. Upon cooling to room temperature the reaction was concentrated by evaporation and then poured into 500ml water. The mixture was acidified and then extracted with methylene chloride until the organic wash no longer indicated product was present. The organic fractions were washed with saturated brine then dried with magnesium sulfate. The solvent was removed under reduced pressure to give a yellow solid. Column chromoatography was performed using 60% ethyl acetate in hexane to give a 70:30 mixture of the product and propylene isomer in 55 % yield as a white solid. Structure and purity were confirmed by ¹H/¹³C NMR and LC-MS.

4) Synthesis of diethyl-2-(hydroxymethyl)-2,3-dihydrothieno[3,4-b]-1,4-dioxine-5,7-dicarboxylic acid

[0044] In a 500 mL round bottom flask equipped with a reflux condenser 11.3 g (0.0357 mol) diethyl 2,3-dihydro-2-(hydroxymethyl)thieno[3,4-b][1,4]dioxine-5,7-dicarboxylate was combined with 12.0 g (0.214 mol) potassium hydroxide in 250 mL water. The reactin mixture was refluxed and the progress of the reaction tracked by TLC. Upon completion of the hydrolysis the reaction was concentrated to -100 mL. The mixture was cooled to 0 C then acidified with concentrated HCl. After allowing to warm to room temperature overnight the white solid was filtered and washed with a small amount of water. Drying under high vacuum gave 8.5 g (90 %) of product as a white solid. Structure and purity were confirmed by ¹H/¹³C NMR and LC-MS.

5) Synthesis of diethyl-2-(hydroxymethyl)-2,3-dihydrothieno[3,4-b]-1,4-dioxin-2-yl methanol

[0045] In a 100 mL round bottom flask, 14.0 g (0.053 mol) of finely powdered 2,3-dihydro-2-(hydroxymethyl)thieno[3,4-b]dioxine-5.7-dicarboxylic acid, 0.42 g copper(II) oxide, and 25 mL quinoline were combined. A reflux condenser was equipped and reaction flask purged with nitrogen. The mixture was heated to 225 C and the reaction traced by TLC. Once all starting material was consumed, the reaction was cooled to room temperature, diluted with ether and filtered. The ether was removed under reduced pressure. The crude product mixture was purified by column chromatography using 30% ethyl acetate in hexane. Upon removal of the solvent 4.4 g (48% yield) of a light yellow oil was isolated. Structure and purity were confirmed by ¹H/¹³C NMR and GC-MS.

EXAMPLE 1: Synthesis of Chloromethyl-3,4-ethylenedioxythiophene for conversion to CDOT-MEOH:

1) 3,4-dimethoxythiophene synthesis from 3,4-dibromothiophene for the improved EDOT-MeOH synthesis:

[0046] Sodium methoxide was prepared by slow addition of small cubes of sodium metal (25 g, 1.05 mol) to ice bath cooled anhydrous methanol (600 mL) in a 1 L 3-necked flask equipped with a reflux condenser under a nitrogen blanket. Between additions of the sodium it was covered in kerosene to exclude moisture. After complete dissolution of the sodium, 50 g (0.207 mol) of 3,4-dibromothiophene, 16.5 g (0.207 mol) copper (II) oxide, and 1.37 g (0.00827 mol) potassium iodide was added to the reaction mixture. The reaction was refluxed for three days. The reaction was then cooled to room temperature and filtered through a sintered glass fritted funnel. The resulting solid was rinsed with ether and the filtrate was poured into 500 mL water. The solution was then extracted with ether. The organic fractions were combined and dried with magnesium sulfate. Solvent removal gave a light yellow oil. Vacuum distillation gave 26.2 g of a clear, colorless oil whose structure and purity were confirmed by ¹H and ¹³C NMR and GC-MS. Yield was 88% of theoretical.

2) Synthesis of 2-(chloromethyl)-2,3-dihydrothieno[3,4-b][1,4]dioxine:

[0047] Under a nitrogen atmosphere in a 500 mL round bottom flask equipped with a reflux condenser, 20.0 g (0.139 mol) dimethoxythiophene, 17.8 g (0.161 mol) 3-chloro-1,2-propanediol, and 5 g p-toluenesulfonic acid was dissolved in 350 mL toluene. The reaction was then heated to ~90 C overnight. At this time TLC indicated consumption of starting material. After cooling the reaction mixture was concentrated to ~100 mL and poured into saturated potassium carbonate solution. The mixture was extracted with DCM and the combined extracts were dried with magnesium sulfate. Solvent removal gave a dark oil that was purified by column chromatography using 3:1 hexanes/DCM. Solvent removal gave the product as a white solid. Structure and purity were confirmed by ¹H/¹³C NMR and LC-MS.

EXAMPLE 2: Conversion of 3,4-dimethoxythiophene to 2-(bromomethyl)-2, 3-dihydrothieno[3,4-b][1,4]dioxine

[0048] Under nitrogen, 20.0 g (0.139 mol) dimethoxythiophene, 25.0 g (0.161 mol) 3-bromo-1,2-propanediol, and 5 g p-toluenesulfonic acid was combined with 350 mL toluene in a 500 mL round bottom flask equipped with a reflux condenser and stir bar. The reaction mixture was sparged with nitrogen for 30 minutes then heated to 100 C overnight. Upon cooling to room temperature the reaction mixture was concentrated to -100 mL and poured into saturated potassium carbonate solution. The resulting solution was extracted with DCM. The combined extracts were washed with brine, then dried with magnesium sulfate. Solvent removal gave a black oil. The crude material was purified by column chromatography using 3:1 hexanes/DCM. Solvent removal gave a white solid that was dried under high vacuum overnight to give 18.6 g of material. The structure and purity were confirmed by ¹H/¹³C NMR and GC-MS. Yield was 57% of theoretical.

EXAMPLE 3: Synthesis of (2,3-dihydrothieno[3,4-b][1,4]dioxin-3-yl)methanol from (2,3-dihydrothieno[3,4-b][1,4]dioxin-2-yl)methyl acetate:

1) Synthesis of (2,3-dihydrothieno[3,4-b][1,4]dioxin-2-yl)methyl acetate (EDOT-MeOAc):

[0049] In a 50 mL Schlenk tube 1.00 g of to 2-(bromomethyl)-2,3-dihydrothieno[3,4-b][1,4]dioxine was combined with 0.5 g (0.0051 mol) potassium acetate and 25 mL DMSO. The tube was sealed and stirred for 1 h at 100 C. At this time TLC indicated complete consumption of starting material. The reaction was poured into water and extracted with ether. After removing the ether under reduced pressure column chromatography was performed using 90% methylene chloride in hexane to isolate a light yellow oil in 90% yield.. The structure and purity were confirmed by ¹H/¹³C NMR and GC-MS.

2) Synthesis of (2,3-dihydrothieno[3,4-b][1,4]dioxin-3-yl)methanol (EDOT-MeOH)

[0050] In a 25 mL round bottom flask equipped with a reflux condenser 0.64 g (0.0030 mol) of (2,3-dihydrothieno[3,4-b][1,4]dioxin-2-yl)methyl acetate was combined with 50% NaOH in water. The reaction was refluxed overnight and then cooled to room temperature. It was then poured into an Erlenmeyer flask filled with 100 mL water. The mixture was acidified then extracted with DCM. The solvent was removed under reduced pressure and column chromatography (7:3 hexanes/ethyl acetate) was performed to give 0.46 g (90%) of product. The structure was confirmed by LC-MS and ¹H/¹³C NMR.

EXAMPLE 4: Synthesis of EDOT-MeOH from EDOT-Methyl-Benzoate:

1) Synthesis of (2,3-dihydrothieno[3,4-b][1,4]dioxin-3-yl)methyl benzoate:

[0051] In a 100 mL round bottom flask 9.00 g (0.0382 mol) 2-(bromomethyl)-2,3-dihydrothieno[3,4-b][1,4]dioxine, 6.39 g (0.0459 mol) ammonium benzoate, and 55 g DMSO were combined. A reflux condenser was equipped and the reaction was heated to 100 C overnight. After cooling to room temperature, the reaction mixture was poured into water and the product was extracted with methylene chloride. The organic fractions were combined and the solvent removed under reduced pressure. Purification by column chromatography provided 7.5 g (71% yield) of a white solid whose structure was confirmed by 1H/13C NMR and LC-MS.

2) Synthesis of (2,3-dihydrothieno[3,4-b][1,4]dioxin-3-yl)methanol:

[0052] In a 100 mL round bottom flask, 7.5 g (0.027 mol) (2,3-dihydrothieno[3,4-b][1,4]dioxin-3-yl)methyl benzoate was dissolved in a minimal amount of warm ethanol and dropwise added to a refluxing solution of 4.58 g (0.081 mol) potassium hydroxide in 50 mL water. After heating overnight, the reaction was cooled to room temperature and acidified to pH 7 by dropwise addition of concentrated hydrochloric acid. The reaction mixture was extracted with methylene chloride. The organic fractions were combined and the solvent removed under reduced pressure. Purification by column chromatography provided 3.95 g (85% yield) of (2,3-dihydrothieno[3,4-b][1,4]dioxin-3-yl)methanol. Structure was confirmed by 1H/13C NMR and LC-MS.

EXAMPLE 5: Synthesis of EDOT-MeOH from Chloromethyl-EDOT (from a carboxylic acid salt to form an ester and subsequent cleaving of the ester linkage with Potassium Hydroxide):

[0053] Chloromethyl-EDOT will be reacted with a carboxylic acid salt, e.g. Acetate, heated to 100-140°C in a polar/aprotic solvent, e.g. DMF, DMAc or DMSO. The resulting ester will then be cleaved easily by using a typical base saponification, e.g. 1% KOH in MeOH/H₂O or with transesterification using an Acid or a base in the presence of MeOH.

EXAMPLE 10: Solubility comparison between EDOT-MeOH and EDOT:

[0054] EDOT (2,3,-dihydrothieno[3,4-b]-1,4-dioxin) monomer purchased from Aldrich Advance Science Company (Mitwaukee, USA) and EDOT-MeOH made in Example 5were tested for solubility in water at room temperature which is about 23°C. EDOT has solubility less than 0.4% (w/w), but EDOT-MeOH has solubility of 1.4% (w/w). The improvement is more than sufficient to facilitate polymerization at the concentration illustrated in Example 11.

Claims

1. A process for preparing a compound of Formula I:

comprising contacting a compound of Formula II:

wherein n is from 1 to 4 and X is halogen; with an inorganic hydroxide, alkali metal carboxylate, alkaline earth metal carboxylate, ammonium carboxylate, or alkylammonium carboxylate.

2. The process of claims 1 wherein the inorganic hydroxide is an alkali metal hydroxide, alkaline earth metal hydroxide, ammonium hydroxide, or alkylammonium hydroxide.

3. The process of claim 1 wherein X is chloro or bromo.

4. The process of claim 1 wherein inorganic hydroxide is KOH, NaOH, LiOH, Mg(OH)₂, Ca(OH)₂, NH₄OH, NR₄OH, or a combination thereof.

5. The process of claim 1 wherein said contacting is performed in the presence of a catalyst.

6. The process of claim 5 wherein the catalyst is a crown ether, a cryptand, sodium iodide, or a combination thereof.

7. The process of claim 1 wherein the carboxylate is sodium acetate, potassium acetate, ammonium acetate, sodium benzoate, potassium benzoate, ammonium benzoate, or a combination thereof.

8. The process of claim 1 comprising contacting a compound of Formula IV

wherein X is halogen, with an inorganic hydroxide to provide a compound of Formula III:

9. The process of claim 8 wherein the compound of Formula IV is produced by contacting 3,4,-alkylenedioxythiophene with 3-halo-1,2-propanediol in the presence of an acid to provide a compound of Formula IV.

10. A process for preparing a compound of Formula II:

wherein X is halogen and n is from 1 to 4, comprising contacting a 3,4-dialkoxythiophene with a halo-1,2-alkanediol in the presence of an acid.

11. The process of claim 10 wherein n is I and the halo-1,2-alkanediol is a 3-halo-1,2-propanediol.

12. The process of claim 10 wherein the acid is para-toluenesulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid, tifluoroacetic acid, sulfuric acid, or a combination thereof.

13. the process of claim 10 wherein said contacting is performed under an inert atmosphere of argon or nitrogen.

14. The process of claim 10 wherein said contacting is performed in the presence of a solvent.

15. The process of claim 14 wherein the solvent is an aralkane.

16. A process for preparing a compound of Formula I comprising the steps of

i) contacting a 3,4-dialkoxythiophene with a halo-1,2-alkanediol in the presence of an acid to form a compound of Formula II:

wherein X is halogen and n is from 1 to 4; and

ii) contacting a compound a Formula II with an inorganic hydroxide, alkali metal carboxylate, alkaline earth metal carboxylate, or ammonium or alkylammonium carboxylate, to form a compound of Formula I wherein n is from 1 to 4:

17. The process of claim 16 wherein the 3,4-dialkoxythiophene is prepared by contacting a 3,4-dihalothiophene with an alkoxide in the presence of a copper and iodine containing reagents.

18. The process of claim 17 wherein the step of contacting is performed under an inert atmosphere of argon or nitrogen.

19. The process of claim 17 wherein the step of contacting a 3,4-dihalothiophene with an alkoxide is performed in the presence of a solvent.

Ansprüche

1. Verfahren zum Herstellen einer Verbindung der Formel I:

umfassend das Kontaktieren einer Verbindung der Formel II:

wobei n 1 bis 4 beträgt und X Halogen ist, mit einem anorganischen Hydroxid, Alkalimetallcarboxylat, Erdalkalimetallcarboxylat, Ammoniumcarboxylat oder Alkylammoniumcarboxylat.

2. Verfahren nach Anspruch 1, wobei das anorganische Hydroxid ein Alkalimetallhydroxid, Erdalkalimetallhydroxid, Ammoniumhydroxid oder Alkylammoniumhydroxid ist.

3. Verfahren nach Anspruch 1, wobei X Chlor oder Brom ist.

4. Verfahren nach Anspruch 1, wobei das anorganische Hydroxid KOH, NaOH, LiOH, Mg(OH)₂, Ca(OH)₂, NH₄OH, NR₄OH oder eine Kombination davon ist.

5. Verfahren nach Anspruch 1, wobei das Kontaktieren in Gegenwart eines Katalysators durchgeführt wird.

6. Verfahren nach Anspruch 5, wobei der Katalysator ein Kronenether, Cryptand, Natriumiodid oder eine Kombination davon ist.

7. Verfahren nach Anspruch 1, wobei das Carboxylat Natriumacetat, Kaliumacetat, Ammoniumacetat, Natriumbenzoat, Kaliumbenzoat, Ammoniumbenzoat oder eine Kombination davon ist.

8. Verfahren nach Anspruch 1, umfassend das Kontaktieren einer Verbindung der Formel IV

wobei X Halogen ist, mit einem anorganischen Hydroxid, um eine Verbindung der Formel III:

bereitzustellen.

9. Verfahren nach Anspruch 8, wobei die Verbindung der Formel IV durch Kontaktieren von 3,4-Alkylendioxythiophen mit 3-Halo-1,2-propandiol in Gegenwart einer Säure hergestellt wird, um eine Verbindung der Formel IV bereitzustellen.

10. Verfahren zum Herstellen einer Verbindung der Formel II:

wobei X Halogen ist und n 1 bis 4 beträgt, umfassend das Kontaktieren eines 3,4-Dialkoxythiophens mit einem Halo-1,2-alkandiol in Gegenwart einer Säure.

11. Verfahren nach Anspruch 10, wobei n 1 beträgt und das Halo-1,2-alkandiol ein 3-Halo-1,2-propandiol ist.

12. Verfahren nach Anspruch 10, wobei die Säure para-Toluolsulfonsäure, Methansulfonsäure, Trifluormethansulfonsäure, Trifluoressigsäure, Schwefelsäure oder eine Kombination davon ist.

13. Verfahren nach Anspruch 10, wobei das Kontaktieren unter einer inerten Atmosphäre von Argon oder Stickstoff durchgeführt wird.

14. Verfahren nach Anspruch 10, wobei das Kontaktieren in Gegenwart eines Lösungsmittels durchgeführt wird.

15. Verfahren nach Anspruch 14, wobei das Lösungsmittel Aralkan ist.

16. Verfahren zum Herstellen einer Verbindung der Formel I, umfassend die Schritte des

i) Kontaktierens eines 3,4-Dialkoxythiophens mit einem Halo-1,2-alkandiol in Gegenwart einer Säure, um eine Verbindung der Formel II zu bilden:

wobei X Halogen ist und n 1 bis 4 beträgt; und

ii) Kontaktierens einer Verbindung der Formel II mit einem anorganischen Hydroxid, Alkalimetallcarboxylat, Erdalkalimetallcarboxylat oder Ammonium- oder Alkylammoniumcarboxylat, um eine Verbindung der Formel I zu bilden,
wobei n 1 bis 4 beträgt:

17. Verfahren nach Anspruch 16, wobei das 3,4-Dialkoxythiophen durch Kontaktieren eines 3,4-Dihalothiophens mit einem Alkoxid in Gegenwart eines Kupfer und Iod enthaltenden Reagens hergestellt wird.

18. Verfahren nach Anspruch 17, wobei der Schritt des Kontaktierens unter einer inerten Atmosphäre von Argon oder Stickstoff durchgeführt wird.

19. Verfahren nach Anspruch 17, wobei der Schritt des Kontaktierens eines 3,4-Dihalothiophens mit einem Alkoxid in Gegenwart eines Lösungsmittels durchgeführt wird.

Revendications

1. Procédé de préparation d'un composé de formule I:

comprenant la mise en contact d'un composé de formule II:

dans laquelle n prend la valeur de 1 à 4 et X est un halogène; avec un hydroxyde inorganique, un carboxylate de métal alcalin, un carboxylate de métal alcalino-terreux, un carboxylate d'ammonium ou un carboxylate d'alkylammonium.

2. Procédé selon la revendication 1, dans lequel l'hydroxyde inorganique est un hydroxyde de métal alcalin, un hydroxyde de métal alcalino-terreux, un hydroxyde d'ammonium ou un hydroxyde d'alkylammonium.

3. Procédé selon la revendication 1, dans lequel X est le chlore ou le brome.

4. Procédé selon la revendication 1, dans lequel l'hydroxyde inorganique est KOH, NaOH, LiOH, Mg(OH)₂, Ca(OH)₂, NH₄OH, NR₄OH ou leur combinaison.

5. Procédé selon la revendication 1, dans lequel ladite mise en contact est effectuée en présence d'un catalyseur.

6. Procédé selon la revendication 5, dans lequel le catalyseur est un éther couronne, un agent cryptant, un iodure de sodium ou leur combinaison.

7. Procédé selon la revendication 1, dans lequel le carboxylate est l'acétate de sodium, l'acétate de potassium, l'acétate d'ammonium, le benzoate de sodium, le benzoate de potassium, le benzoate d'ammonium, ou leur combinaison.

8. Procédé selon la revendication 1, comprenant la mise en contact d'un composé de formule IV

dans laquelle X est un halogène, avec un hydroxyde inorganique pour fournir un composé de formule III:

9. Procédé selon la revendication 8, dans lequel le composé de formule IV est produit par la mise en contact de 3,4,-alcylènedioxythiophène avec du 3-halogéno-1,2-propanediol en la présence d'un acide pour fournir un composé de formule IV.

10. Procédé de préparation d'un composé de formule II:

dans laquelle X est un halogène et n prend la valeur de 1 à 4, comprenant la mise en contact d'un 3,4-dialcoxythiophène avec un halogéno-1,2-alcanediol en la présence d'un acide.

11. Procédé selon la revendication 10, dans lequel n a la valeur de 1 et l'halogéno-1,2-alcanediol est un 3-halogéno-1,2-propanediol.

12. Procédé selon la revendication 10, dans lequel l'acide est l'acide paratoluènesulfonique, l'acide méthanesulfonique, l'acide trifluorométhanesulfonique, l'acide trifluoroacétique, l'acide sulfurique, ou leur combinaison.

13. Procédé selon la revendication 10, dans lequel ladite mise en contact est effectuée sous une atmosphère inerte d'argon ou d'azote.

14. Procédé selon la revendication 10, dans lequel ladite mise en contact est effectuée en la présence d'un solvant.

15. Procédé selon la revendication 14, dans lequel le solvant est un aralcane.

16. Procédé de préparation d'un composé de formule I, comprenant les étapes de

i) mise en contact d'un 3,4-dialcoxythiophène avec un halogéno-1,2-alcanediol en la présence d'un acide pour former un composé de formule II:

dans laquelle X est un halogène et n prend la valeur de 1 à 4; et

ii) mise en contact d'un composé de formule II avec un hydroxyde inorganique, un carboxylate de métal alcalin, un carboxylate de métal alcalino-terreux ou un carboxylate d'ammonium ou d'alkylammonium, pour former un composé de formule I,
dans laquelle n prend la valeur de 1 à 4:

17. Procédé selon la revendication 16, dans lequel le 3,4-dialcoxythiophène est préparé par mise en contact d'un 3,4-dihalogénothiophène avec un alcoxyde en la présence de réactifs contenant du cuivre et de l'iode.

18. Procédé selon la revendication 17, dans lequel l'étape de mise en contact est effectuée sous une atmosphère inerte d'argon ou d'azote.

19. Procédé selon la revendication 17, dans lequel l'étape de mise en contact de 3,4-dihalogénothiophène avec un alcoxyde est effectuée en la présence d'un solvant.